Key pointsr Inositol-1,4,5-trisphosphate receptors (IP 3 Rs) modulate pacemaking in embryonic heart, but their role in adult sinoatrial node (SAN) pacemaking is uncertain. r These findings support development of IP 3 signalling modulators for regulation of heart rate, particularly in heart failure where IP 3 Rs are upregulated.Abstract Cardiac pacemaking initiated by the sinus node is attributable to the interplay of several membrane currents. These include the depolarizing 'funny current' (I f ) and the sodium-calcium exchanger current (I NCX ). The latter is activated by ryanodine receptor (RyR)-mediated calcium (Ca 2+ ) release from the sarcoplasmic reticulum (SR). Another SR Ca 2+ release channel, the inositol-1,4,5-triphosphate receptor (IP 3 R), has been implicated in the generation of spontaneous Ca 2+ release in atrial and ventricular cardiomyocytes. Whether IP 3 R-mediated Ca 2+ release also influences SAN automaticity is controversial, in part due to the confounding influence of periodic Ca 2+ flux through the sarcolemma accompanying each beat. We took advantage of atrial-specific sodium-calcium exchanger (NCX) knockout (KO) SAN cells to study the influence of IP 3 signalling on cardiac pacemaking in a system where periodic intracellular Ca 2+ cycling persists despite the absence of depolarization or Ca 2+ flux across the sarcolemma. We recorded confocal line scans of spontaneous Ca 2+ release in WT and NCX KO SAN cells in the presence or absence of an IP 3 R blocker (2-aminoethoxydiphenyl borate, 2-APB), or during block of IP 3 production by the phospholipase C inhibitor U73122. 2-APB and U73122 decreased the frequency of spontaneous Ca 2+ transients and waves in WT and NCX KO cells, respectively. Alternatively, increased IP 3 production induced by phenylephrine increased Ca 2+ transient and wave frequency. We conclude that IP 3 R-mediated SR Ca 2+ flux is crucial for initiating and modulating the RyR-mediated Ca 2+ cycling that regulates SAN pacemaking. Our results in NCX KO SAN cells also demonstrate that RyRs, but not NCX, are required for IP 3 to modulate Ca 2+ clock frequency.

Objectives: To analyze the demographics and socioeconomic status of the morbidly obese ovarian cancer patients in the United States. Methods: Data were extracted on all ovarian cancer patients from the National Inpatient Survey in 2010. Morbidly obese women were identified using the ICD-9 diagnostic codes. Chi-square, t-test, and ANOVA tests were used in statistical analyses. Results: Among the 5401 ovarian cancer patients, the median age was 61 years (range, 18 to 101 years) and the majority were white (77%). Most of the women were insured by Medicare or a private insurance (41% and 46%, respectively); the remainder had Medicaid or were uninsured (9% and 5%, respectively). A total of 211 women (4%) were identified as being morbidly obese. Morbidly obese patients were younger than the non-morbidly obese (median 56 years vs 61 years, P b 0.01). Additionally, Native Americans, blacks, and Hispanics were more likely to be morbidly obese compared to whites and Asians (10%, 7%, and 4% vs 2% and 1%, respectively, P b 0.01). Morbidly obese patients were more likely to be insured by Medicaid than by a private insurance, Medicare, or were uninsured (7% vs 4%, 3%, and 2%, respectively, P b 0.01). Moreover, morbidly obese patients were more likely to have a lower income (5% vs 3%, P b 0.01). The morbidly obese had the same average length of stay as the non-morbidly obese (8 days vs 8 days, P = 0.26). There were no significant differences between the morbidly obese and non-morbidly obese based on hospital volume, region of the United States, and academic vs community institution. Conclusions: Morbidly obese ovarian cancer patients were more likely to be younger, of lower socioeconomic class, and have Medicaid insurance. Characterizing the morbidly obese patients with ovarian cancer may allow for focused preventive strategies and better allocation of resources to care for these vulnerable patients.Objectives: Obesity may negatively influence tumor biology in women with epithelial ovarian cancers. To date, only body mass index (BMI) determined at the time of diagnosis has correlated with clinical outcome. We hypothesized that obesity negatively affects survival throughout the disease course and sought to determine the prognostic role of BMI at the time of secondary cytoreductive surgery (SCS) for recurrent ovarian cancer.Methods: We performed a retrospective institutional review boardapproved review of patients undergoing SCS for recurrent epithelial ovarian or peritoneal cancer between 1997 and 2012. We abstracted data that included patient height, weight at SCS, age, and clinical outcome. Statistical analyses included Fisher's exact test, Kaplan-Meier survival, and Cox regression analysis. Results: We identified 104 patients; 2% were underweight (BMI b18.5), 45% were of ideal body weight (BMI ≥18.5 to b25), 30% were overweight (BMI ≥25 to b30), and 23% were obese (BMI ≥30). There were no differences in age or incidence of hypertension, diabetes, coronary artery disease, or venous thromboembolism among the BMI strata. Overall...